The Advanced Research Projects Agency for Health (ARPA-H), which operates under the U.S. Department of Health and Human Services, is making contract awards of up to $125 million to five teams to build a nationwide network for producing “made-to-order” ribonucleic acid (RNA)-based genetic medicines on demand.  

The goal is to develop “automated, distributed biomanufacturing technology that doesn’t currently exist — designed to increase access to genetic medicines for all Americans.” The funding is part of the ARPA-H’s Genetic Medicines and Individualized Manufacturing for Everyone (GIVE) program, which aims to enable a multi-site, multi-product, and multi-scale biomanufacturing network.

“Genetic medicines require centralized, specialized production that is traditionally slow and expensive, and cold-chain logistics keep patients waiting or without access altogether,” according to GIVE, which notes that requirements for ultracold storage and shipping add to the cost and complexity of manufacturing these drug products, especially for personalized and individualized genetic medicines.

GIVE contends that without innovative manufacturing processes, many products may never advance out of early-stage research and development.

“Personalized treatments like Baby KJ’s revolutionary CRISPR cure currently take months to manufacture, cost hundreds of thousands of dollars, and require years of clinical trials to prove safe and effective,” according to ARPA-H. “If GIVE succeeds, these therapies could be made locally and on demand, in a fraction of the time and cost. Faster manufacturing could, in turn, help trials move more efficiently.”

ARPA-H said the GIVE program will engage the U.S. Food and Drug Administration to co-develop the regulatory framework needed to bring distributed, individualized genetic medicine manufacturing to scale.

Five teams, five approaches

Under the GIVE program, Centillion Biosciences will develop a unified, end-to-end system combining cartridge-based technologies for DNA/RNA manufacturing, integrated fill-finish and quality control testing, as well as digital process management.

Centillion Biosciences’ system “delivers scalable manufacturing (from personalized to large-scale), first-of-its kind measurement technologies, and the data-handling capabilities distributed RNA production requires,” according to ARPA-H’s announcement.

HDT Bio Corporation will develop a platform with an integrated architecture that combines automated DNA synthesis, chip-based RNA production, closed fill-finish, embedded process analytical technologies, and autonomous robotics-enabled quality control testing. ARPA-H noted that for HDT Bio’s platform “manufacturing and quality functions both operate inside a controlled enclosure with compliant electronic batch records.”

Massachusetts General Hospital will develop a single-use, all fluidics chip system and control unit hardware capable of continuous manufacturing and quality-control testing. “By using a closed fluidic path, the system eliminates the need for open-air liquid handling and a cleanroom enclosure, representing a compact, efficient (<3 day), and cost-effective approach to advance distributed manufacturing with minimal hardware investment,” according to ARPA-H.

A University of Utah team will develop an all-in-one genetic medicine testing platform enabling full quality control testing — and lot release — within as little as one day by leveraging digital microfluidics, advanced optics, and artificial intelligence (AI).

Using digital microfluidics, advanced optics, and AI, the platform from the University of Utah team will “perform multi-parametric characterization of therapeutics at nanoliter- to microliter-scales in a compact, single-use cartridges format,” ARPA-H said.

Waterfall Scientific will develop a fully automated, benchtop, continuous-flow system for end-to-end production of RNA drug products, combining proprietary technologies from a consortium of expert organizations and comprising four integrated, modular units — cell-free enzymatic DNA production, continuous-flow RNA synthesis, lipid nanoparticle formulation, and fill-finish.

The Waterfall Scientific team will also develop an integrated quality control system for lot release, combining in-line, at-line and off-line characterization of drug product, fully autonomous and automated using proprietary software, robotics, and what GIVE calls the “most advanced” measurement technologies currently available.

“The breakthrough manufacturing and quality control technologies needed to enable these therapies to reach patients at scale doesn’t exist yet,” GIVE Program Manager John Schiel said in a statement. “This investment will catalyze domestic innovation for distributed manufacturing of RNA-based genetic medicines — and these teams will deliver it in a matter of years, not decades.”

While decentralized manufacturing could improve patient access by addressing issues related to the high cost of production, scale, and distribution, industry stakeholders contend the most likely situation over the next 10 years is a hybrid ecosystem of both the centralized and point-of-care manufacturing models.